TW201032805A - Pharmaceutical compositions comprising a compound having suppressive effect on nutrient digestion or absorption and a cyclohexanecarboxamide derivative - Google Patents

Abstract

It is found that a pharmaceutical composition can meaningly decrease body weight, which comprises a compound having suppressive effect on nutrient digestion or absorption, pharmaceutically acceptable salts or solvates thereof, and a compound represented by the formula (I) (in formula, R1 is alkyl; R2 is hydrogen atom, or alkyl, Z is substituted or non-substituted alkyl, substituted or non-substituted alkenyl, substituted or non-substituted amino, substituted or non-substituted alkoxy, substituted or non-substituted hydrocarbon cyclic group, or substituted or non-substituted heterocyclic group). The said pharmaceutical composition is useful for the treatment or prevention of obesity and the disorders related to obesity.

Description

201032805 VI. Description of the Invention: [Technical Field of the Invention] The present invention relates to a pharmaceutical composition in which a compound having a nutrient absorption and absorption inhibiting action and a cyclohexane formamide derivative are combined. In particular, the present invention and a compound having a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof, or a solvate thereof, and a compound represented by the following formula (I), a pharmaceutically acceptable salt thereof, or the like It is related to the pharmaceutical composition in which the solvate is combined. The pharmaceutical composition is extremely useful for preventing or treating obesity or fat m w fat related diseases.

(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group.) φ [Prior Art] Obesity is defined as the weight relative to fat removal. The state of excess fat or fat tissue in the body is considered to be a major risk factor for health problems. The Body Mass Index (BMI) is a simple index that classifies adults or groups of individuals (over 15 years of age) into height-to-weight ratios that are used together when they are overweight or obese. It is defined as the weight (kg/m2) obtained by dividing the body weight (kg) by the square of the height (meter). The World Health Organization has designated BMI of 25 kg/m2 or more as "overweight" and 30 kg/m2 or more as "obesity". 201032805 On the other hand, the Sakamoto Obesity Society has a BMI of 25 kg/m2 or more as “fat fat”. The reason for this is that the number of patients with obesity-related diseases such as diabetes or dyslipidemia increases with the increase in BMI, and the average number of patients with the disease at a BMI of 25 kg/m2 is 1.0 or more. According to a 2005 survey by the World Health Organization, approximately 1.6 billion people worldwide are overweight and at least 400 million are obese. Obesity is mainly caused by an increase in caloric intake relative to physical activity or daily calorie consumption. In recent years, the number of obese people has increased due to the increase in the intake of high-fat, high-sugar foods. It is predicted that more than 700 million people worldwide will be diagnosed with obesity in 2015. As for the agent for preventing or treating obesity, there are known selective serotonin reuptake inhibitors such as Fenfluramine and Fluoxetin, and Mazindol, etc., having an appetite suppressing effect. A compound that inhibits the absorption and absorption of nutrients. A compound having a nutrient absorption and absorption inhibitory action, such as a compound having an action of inhibiting glucose absorption (α-glucosidase inhibitor, SGLT-2 inhibitor, etc., a compound having a fat absorption inhibitory effect, etc.) has a fat absorption inhibiting action. Compounds such as lipase inhibitors (compounds with gastric lipase inhibition, compounds with pancreatic lipase inhibition, etc.), bile acid adsorption resins, etc. Orlistat is a pancreatic lipase inhibitor Anti-obesity drugs for action. Non-Patent Document 1 reports that the results of clinical trials over the leap period have resulted in more than one-third of obese patients in the orlistat administration group losing more than 10% of their body weight before administration. Compounds with a saccharide absorption inhibitor, Dapafloxacin 201032805 (Dapagliflozin) (SGLT-2 inhibitor) and a compound with a fat absorption inhibitory effect, orlistat (THL), are known to exhibit in addition to the inhibition of weight gain. The hyperactive action (see Non-Patent Document 2, in particular, Fig. 3 and Non-Patent Document 3). Non-Patent Document 4 reports that it is known MK -0557, an NPY Y5 receptor antagonist, did not show significant weight loss in obese patients. This paper strongly suggests that inhibition of NPY Y5 receptor has no significant effect on weight loss. In addition, MK - 0557 has the following structure Expression.

Non-Patent Document 5 reports that the simultaneous administration of orlistat and MK-057 is compared with the single dose of orlistat, and the body weight is not significantly reduced. This literature strongly suggests that inhibition of the NPY Y5 receptor does not increase the weight loss efficiency of orlistat. The use or combination of orlistat and NPY Y5 receptor antagonists is described in Patent Documents 1, 2 and 3. However, the patent documents do not disclose examples or specific data, nor do they disclose or imply actual effects. The compound represented by the formula (1) is known to have an NPY Y5 receptor-specific antagonistic action (see Patent Document 4 and Patent Document 5). 201032805

Wherein R1 is alkyl, R2 is hydrogen or alkyl, Z is unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted amine, substituted or unsubstituted alkoxy A non-patent document 6 in which a substituted cyclic hydrocarbon group or a substituted cyclic hydrocarbon group or a substituted or unsubstituted compound is reported, a compound (a) of a compound represented by the formula (I) in a one-year clinical trial, the administration group is obese The patient showed a 5% or more body weight reduction before administration. The literature 5 describes that the compound represented by the above formula (I) exhibits food intake; and the compound (a) is represented by the following structural formula. (8) However, the pseudonym having the nutrient absorption and absorption inhibition effect (I) The composition of the compound represented by the combination of the compounds is not disclosed or suggested. Prior Art Document Patent Document 1: International Publication No. WO2003/07 25 77 Patent Document 2: International Publication No. WO2004/014884 Patent Literature 3: International Publication No. WO2004/0090 1 Patent Document 4: International Publication No. WO2001/37826 Patent Document 5: International Publication No. WO2006/001 No. 3 No. 1 is substituted or replaced with or substituted with or not ). With the fruit 'the above 匕 1/3 or more. Also, the patent 3 is used for production. And the above documents are all 201032805 Non-Patent Document 1: The Journal of the American Medical Association (1999) 281, 235-242 Non-Patent Document 2: International Journal of Obesity (1987) 1 l, Suppl. 3, 35-42 Non-patent literature 3 : Obesity 15 (Suppl. 9): A121, 2007 Non-Patent Document 4: Cell Metabolism 4, 275-282, 2006 Non-Patent Document 5: 0besity (2007), 15 (8), 2027-2042 φ Non-Patent Document 6: Salt "Yonyigi announces positive top-line efficacy results from year-long studies of velneperit, a novel NPY Y5 receptor antagonist being investigated for the treatment of obesity", [online], February 17, 2011 Yan Yeyi Pharmaceutical, Internet < URL: http://www.shi onogi.co.jp/ir_en /news/detail/e_09 0217-2.pdf >

Non-Patent Document 7: Yan Yeyi Pharmaceutical Co., Ltd., "1st Half and 2nd Quarter of Fiscal 2009 Financial Results", [online], November 5, 2011, Yan Yeyi Pharmaceutical, Internet < URL: http:&quot [www.shionogi.co.jp/ir_en/explanatory/pdf/e_p09 1105.pdf> [Summary of the Invention] [Problem to be Solved by the Invention] An object of the present invention is to provide a very useful one for preventing or treating diseases related to obesity or obesity. Pharmaceutical composition. 201032805 [Method for Solving the Problem] The inventors of the present invention have carefully studied and found the following results. The results of the compound represented by the formula (I) of the compound having the nutrient digestion and absorption inhibitory effect and the cyclohexylamine derivative were used (including the co-administration), and the mice were tested in the obese model to significantly inhibit the body weight in a dose-dependent manner. RVq.nh d%

(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, A substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). Further, when a compound represented by the formula (1) having an ΝΡγ Y5 receptor antagonistic action and a compound having a nutrient absorption and absorption inhibiting action were used, it was found that the weight loss was increased in comparison with the total of the treatments of the respective compounds. That is, unlike the description in Non-Patent Document 5, the weight loss at the time of use is larger than the total treatment of the individual compounds alone. When it is considered that the inhibition of the NPY Y5 receptor does not increase the weight loss efficiency of orlistat in Non-Patent Document 5, the weight loss effect on the addition is not the NPY Y5 receptor antagonism, but is expressed by the formula (I). The specific effect of the compound. The compound having a nutrient absorption and absorption inhibiting action is described in Non-Patent Document 2, Non-Patent Document 3, etc., and exhibits a function of suppressing weight gain on the one hand and a hyperfeeding action on the other hand. Further, the present inventors have found that a compound having a nutrient absorption and absorption inhibiting action and a compound represented by the formula (I) can inhibit the feeding action caused by a compound having a nutrient absorption and absorption inhibiting action in 201032805. Therefore, when the pharmaceutical composition of the present invention is compared with a single agent having a nutrient absorption and absorption inhibiting action, it is possible to exhibit a very strong body weight reducing effect. Therefore, the pharmaceutical composition of the present invention is very useful as a therapeutic or prophylactic agent for obesity. That is, the present invention relates to the following items. (1) A pharmaceutical composition which is a compound having a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof or a solvate thereof, and a compound represented by the formula (I) and a pharmaceutically acceptable salt thereof or a pharmaceutical composition obtained by combining the solvates thereof;

(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, A substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). (2) The pharmaceutical composition according to the item (1), wherein the pharmaceutical composition is a compounding agent. (3) The pharmaceutical composition according to the item (1), which is a pharmaceutical composition containing a compound having a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof, or a solvate thereof, and a formula ( I) a kit of the indicated compound and its pharmaceutically acceptable salt or its solvate; 10-201032805

NZ 〇) (wherein R 1 is an alkyl group, R 2 is a hydrogen atom or an alkyl group, and Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, substituted or substituted Amino group, substituted or unsubstituted alkoxy group, substituted or substituted cyclic hydrocarbon group, or substituted or unsubstituted heterocyclic group). (4) The pharmaceutical composition according to any one of (1) to (3), wherein the compound having a nutrient absorption and absorption inhibiting action is a compound having a fat absorption inhibiting action. (5) The pharmaceutical composition according to the item (4), wherein the compound having a fat absorption inhibiting action is a compound having a sputum lipase inhibiting action. (6) The pharmaceutical composition according to the item (5), wherein the compound having pancreatic lipase inhibitory action is orlistat. The pharmaceutical composition according to any one of the items (1) to (6), wherein the compound represented by the formula (I) is a compound represented by the following formula (a).

(8) The pharmaceutical composition according to any one of the items (1) to (7) for use in the prevention or treatment of obesity or obesity-related diseases or weight management of obesity (9) as in (8) The pharmaceutical composition described in which obesity-related diseases are Addephagia, hypertension, impaired glucose tolerance, diabetes, metabolic syndrome, abnormal fat metabolism, arteriosclerosis, hyperuricemia, -11 - 201032805 gout, fat Liver, endometrial cancer, breast cancer, prostate cancer, colorectal cancer, osteoarthritis, low back pain, obstructive sleep-absorptive syndrome, coronary artery disease, cerebral infarction, menstrual abnormalities, Predwell's syndrome (Prader) -Willi Syndrome), Froehlich Syndrome, or Pickwickian Syndrome. (10) An agent for enhancing the prophylactic or therapeutic effect of an obesity or obesity-related disease, which comprises a compound represented by the formula (I), a pharmaceutically acceptable salt thereof or a solvate thereof;

(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group, and a compound having a nutrient absorption and absorption inhibiting effect and a pharmaceutically acceptable amount thereof An agent of a salt or a solvate thereof. (11) An agent for enhancing the prophylactic or therapeutic effect of an obesity or obesity-related disease of a medicament, which comprises a compound represented by the formula (I) and a pharmaceutically acceptable salt thereof or a solvate thereof;

(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, substituted or not substituted by -12-201032805 An amine group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group; and a compound having a nutrient absorption and absorption inhibiting action and A pharmaceutically acceptable salt or a solvate thereof. (12) A pharmaceutical agent comprising a compound having a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof, or a solvate thereof, which is used in combination with a compound represented by the formula (I) and a pharmaceutically acceptable compound thereof The use of a salt or a solvent thereof;

(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, A substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). (13) A pharmaceutical agent comprising a compound represented by the formula (I), a pharmaceutically acceptable salt thereof, or a solvate thereof, which is used in combination with a compound having a nutrient absorption and absorption inhibiting effect and a pharmaceutically acceptable substance thereof The use of a salt or a solvate thereof;

NZ (I) (wherein R 1 is an alkyl group, R 2 is a hydrogen atom or an alkyl group, and Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, substituted or not - 13- 201032805 A substituted amino group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). (14) The agent according to Item (12) or (13), which is used for the prevention or treatment of obesity or obesity-related diseases or the weight management of obesity. Furthermore, the following invention is also included in the scope of the invention. (15) A method for preventing or treating obesity or obesity-related diseases or a method for managing body weight of obesity, which comprises a compound having a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof, or the like a step of administering a compound represented by the formula (I) and a pharmaceutically acceptable salt thereof or a solvate thereof;

(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, A substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). (16) a compound having a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof, or a solvate thereof, and a compound represented by the formula (I), and a pharmaceutically acceptable salt thereof or a solvate thereof, For the manufacture of a pharmaceutical composition for the prevention or treatment of obesity or obesity-related diseases or weight management of obesity; -14- 201032805

Ο) (wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group a substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). (17) A method for inducing or promoting weight loss, or maintaining or managing body weight, comprising a compound having a nutrient absorption and absorption inhibiting action and a pharmaceutically acceptable salt thereof or a solvate thereof and the like (I) a step of administering a combination of the indicated compound and a pharmaceutically acceptable salt thereof or a solvate thereof;

RkNHV^ ° 0 . ΌγΝ-ζ 0) (wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, and hydrazine is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, A substituted or unsubstituted amino group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). (18) a compound having a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof, or a solvate thereof, and a compound represented by the formula (I), and a pharmaceutically acceptable salt thereof or a solvate thereof, For the manufacture of a pharmaceutical composition for inducing or promoting weight loss, & maintenance or management; -15- 201032805 Ν-Ζ (I) τχχχ (wherein R1 is a hospital base 'R2 is a hydrogen atom or a substituent, Ζ is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). (19) A pharmaceutical composition which is a compound which inhibits or promotes weight loss, or maintains or manages body weight, and which has a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof, or the like, and a formula (I) a combination of the indicated compound and its pharmaceutically acceptable salt or its solvate;

(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, hydrazine is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, A substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). (20) A method for enhancing the prophylactic or therapeutic effect of an obesity or obesity-related disease containing a compound having a nutrient absorption and absorption inhibiting action and a pharmaceutically acceptable salt thereof or a solvate thereof, which comprises a formula ( 1) a pharmaceutical step of expressing a compound and a pharmaceutically acceptable salt thereof or a solvate thereof; -16- 201032805

(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, and Z is a substituted/unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or substituted amino group, A substituted or unsubstituted alkoxy group, a substituted or substituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). (21) The use of a compound represented by the formula (I) and a pharmaceutically acceptable salt thereof, and the like, for use in the manufacture of a compound having a nutrient absorption inhibition effect and a pharmaceutically acceptable salt thereof or a strong agent for preventing or treating the obesity or obesity-related diseases of the agent of the lysate H compound;

(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, A substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). (22) a compound represented by the formula (I), a pharmaceutically acceptable salt thereof or a solvate thereof, which is used for enhancing a compound having a nutrient absorption and absorption inhibiting action and a pharmaceutically acceptable salt thereof or The preventive or therapeutic effect of obesity or obesity-related diseases of solvate-like agents; -17- 0) 201032805

(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, A substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). (2 3) A method for enhancing the prophylactic or therapeutic effect of an obesity or obesity-related disease containing a compound represented by the formula (I) and a pharmaceutically acceptable salt thereof or a solvate thereof, which comprises a nutrient a step of administering a compound which inhibits digestion and absorption and a pharmaceutically acceptable salt thereof or a solvate thereof; RVNH, r^ R2 cfb 〇) ο (wherein R1 is an alkyl group, and R2 is a hydrogen atom or an alkyl group, Ζ is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted amino, substituted or unsubstituted alkoxy, substituted or unsubstituted a cyclic hydrocarbon group or a substituted or unsubstituted heterocyclic group). (24) A use of a compound having a nutrient absorption and absorption inhibiting action and a pharmaceutically acceptable salt thereof or a solvate thereof, which is used for producing a compound represented by the formula (I) and a pharmaceutically acceptable salt thereof Or an agent for the prevention or treatment of obesity or obesity-related diseases of a solvent & medicinal agent; -18- 201032805 NZ (I) ^Hv〇/ ο (wherein R1 is an alkyl group and R2 is a hydrogen group Atom or alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, a substituted or unsubstituted alkoxy group, substituted Or an unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). (25) a compound having a nutrient absorption and absorption inhibiting action and a pharmaceutically acceptable salt thereof or a solvate thereof, which is used for enhancing a compound represented by the formula (I) and a pharmaceutically acceptable salt thereof or The preventive or therapeutic effect of an obesity or obesity-related disease of a solvate thereof;

(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted aryl group, A substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). (26) A method for producing a pharmaceutical composition according to the item (1), which is characterized in that a compound having a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof, or a solvate thereof, and the like are Mixing the compound represented by I) and its pharmaceutically acceptable salt or its solvate;

-19- 201032805 (wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted substituted amine group , a substituted or unsubstituted alkoxy group, a substituted or substituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). [Effect of the Invention] The pharmaceutical composition of the present invention is very useful as a gastric or prophylactic agent for obesity or obesity-related diseases. Moreover, the pharmaceutical composition is very useful in the management of obesity. [Embodiment] The present invention is a compound for preventing or treating obesity, such as a compound having a sugar absorption inhibiting action and a compound having a fat absorption inhibiting action. Examples of the compound having a sugar absorption-inhibiting action include a compound α-glucoside glucosidase inhibitor (Acarbose, Voglibose, etc.; Journal 1 18:340-346 (2001), Pharmacology Biochemistry

Behavior 1 9:7 1 -78( 1 9 83)), a SGLT-2 inhibitor that inhibits the reabsorption of carbohydrates by the kidney (Dapagliflozin, Remogliflozin, KGT-1075, etc; Journal of Medicinal Chemistry 52(7): 1 7 85 - 1 794 (2009)) and so on. The "compound having a nutrient absorption and absorption inhibiting action" in the present application is preferably a compound such as Dapagliflozin, Remogliflozin, or a compound having a fat absorption inhibitory effect, -20-201032805. The "compound having a fat absorption inhibiting action" includes a lipase inhibitor (a compound having a gastric lipase inhibiting action, a compound having a pancreatic lipase inhibiting action, etc.), a cholic acid binding resin, and the like. The "cholate-binding resin" includes Colestyramine, Colestyramide, and the like. Colestyramine and C'olestyramide are anion exchange resins that bind to bile acids in the digestive organs to inhibit absorption of fat (Expert Opinion on Investigational Drugs 15:1337-51 (2006)) . "Compound having pancreatic lipase inhibition" includes Orlistat, Lipstatin, Panclicin, Cetilistat, and the like. Nibastatin (U.S. Patent No. 4,598,089) is a natural product derived from microorganisms, and Orlistat is a hydrogenated linorestatin. Panlinsi is an analogue of Orlistat (Journal of Antibiotics 47(12): 1 369-1 375 (1 994). The new lysine has a different chemical structure than Orlistat. "Current Opinion in Investigational Drugs 9: 414-21 (2008)." Orlistat is a traditional compound that controls or prevents obesity and dyslipidemia. 3S,4S) - 3 -Hexyl-4 -[(2S)-2-hydroxytridecyl]-2-oxobutanone N-methylindenyl-L-leucine. About Orlistat The weight-inhibiting action of (Orlistat) is described in Non-Patent Document 1. Orlistat (Orlistat) manufacturing method, Pharmacy-21-201032805, etc., as described below, U.S. Patent No. 4,598,089, U.S. Patent No. 5,246,960, Patent No. 4,931,463, U.S. Patent No. 5,175, 186, U.S. Patent No. 4,983,746, U.S. Patent No. 5,245, 056, U.S. Patent No. 5,399, 720, International Publication No. WO97/032409, International Publication No. WO 00/0 9122 , International Publication No. WO00/09 No. 123, European Patent No. 524495. "Compound having a nutrient absorption and absorption inhibiting effect" exhibits a hyperpigmentation action in addition to the digestion and absorption inhibiting action of nutrients. Non-Patent Document 3 describes Dapaver having a sugar absorption inhibiting action. In addition to the effect of suppressing the increase in body weight, it also exhibits hypersensitivity. In addition, Non-Patent Document 2 describes that Orlistat, which has a fat absorption-inhibiting effect, exhibits hypersensitivity in addition to the effect of suppressing body weight gain. The cyclohexanecarbamamine derivative of the pharmaceutical composition of the present invention is a compound represented by the formula (I), a pharmaceutically acceptable salt thereof or a solvate thereof.

(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, A substituted or unsubstituted alkoxy group, a substituted or substituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). The alkyl group is a linear or branched alkyl group having 1 to 10 carbon atoms. Package t -22- 201032805 Alkyl group having 1 to 6 carbon atoms, a group having a carbon number of 1 to 4, an alkyl group having 1 to 3 carbon atoms, and the like. Such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, secondary butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, hexyl, isohexyl, N-heptyl, isoheptyl, n-octyl, isooctyl, n-decyl, n-decyl and the like. R1 is preferably isopropyl or tertiary butyl. a substituent of "alkyl" such as (1) halogen; ^(2) cyano; © (3) may be substituted by one or more substituents selected from the group of substituents/5 as defined below ( i) a hydroxyl group, (ii) an alkoxy group, (iii) a thiol group, (iv) an alkylthio group, (v) a mercapto group, (vi) a decyloxy group, a (vii) carboxyl group, a (viii) alkoxycarbonyl group, (ix) imine group, (X) amine carbenyl group, UO thiamine carbenyl group, alkylamine carbenyl group, (xiii) alkylthiocarbamyl group, (xiv) amine group, (xv) alkylamino group Or (xvi) a heterocyclic carbonyl group or the like. The substituent group Θ is a halogen, a protected hydroxyl group, a thiol group, a decyloxy group, an alkenyl group, an amine group, an alkylamino group, an alkoxycarbonylamino group, an alkylthio group, a decyl group, a carboxyl group, an alkoxy group. A carbonyl group, an amine carbenyl group, a cyano group, a cycloalkyl group, a phenyl group, a phenoxy group, an alkylphenyl group, an alkoxyphenyl group, a halogenated phenyl group, a naphthyl group, and a heterocyclic group. The "alkenyl group" is a linear or branched alkenyl group having 2 or more carbon atoms having one or more double bonds at any position. It contains an alkenyl group having 2 to 8 carbon atoms and an alkenyl group having 3 to 6 carbon atoms. Such as vinyl, propenyl, isopropenyl, butenyl, isobutenyl, prenyl, butadienyl, pentenyl, isopentenyl, -23- 201032805 pentadienyl, Alkenyl, isohexenyl, hexadienyl, heptenyl, octenyl, nonenyl, decenyl and the like. a substituent of "alkenyl" such as halogen, alkoxy, alkenyl, amino, alkylamino, alkoxycarbonyl, alkylthio, decyl, carboxy, alkoxycarbonyl, amidyl, One or more substituents such as a cyano group, a cycloalkyl group, a phenyl group, an alkylphenyl group, an alkoxyphenyl group, a naphthyl group, and a heterocyclic group are used. The "alkoxy group" is a group in which the above "alkyl group" is bonded to an oxygen atom. Specifically, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, di-butoxy, tert-butoxy, n-pentyloxy, isopentyloxy Base, neopentyloxy, hexyloxy, isohexyloxy, n-heptyloxy, isoheptyloxy, n-octyloxy, isooctyloxy and the like. The substituent of the "alkoxy group" is preferably one or more substituents selected from the group consisting of the above substituent groups; and a phenyl group, an alkylphenyl group, an alkoxyphenyl group, a naphthyl group, and a heterocyclic group. "Honey Sulphur", "Honey Alkyl", "Professional Acetone", "Amiline J", "Ya Sulfogen", "Sulphuric Acid", "Amine Dilatation" The alkyl group of the "base", "hydroxyl group", "alkylphenyl", "alkoxyalkyl", "dentated alkyl" or "phenylthio" is the same as the above "thiol". The alkyl moiety of "alkoxycarbonyl", "alkoxyalkyl", "alkoxycarbonylamino", "homoyloxyphenyl" or "phenylalkoxy" is the same as the above "alkyl group". The substituent of the "amino group" is, for example, substituted or unsubstituted from the above substituent group, a benzoinyl group of the substituent -24-32,830,805 or a substituted or unsubstituted heterocyclic carbonyl group (wherein the substituent is selected from a hydroxyl group, an alkyl group) One or more substituents selected from one or more substituents of an alkoxy group or an alkylthio group. The "cycloalkyl group" includes "cycloalkyl group", "cycloalkenyl group", "bicycloalkyl group", and "aryl group". The "cycloalkyl group" is a cyclic alkyl group having 3 to 8 carbon atoms. Contains a 5 or 6 cyclic alkyl group. Such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, _ and cyclooctyl and the like. The "cycloalkenyl group" has one or more double bonds at any position in the ring of the above cycloalkyl group. For example, a cyclopropenyl group, a cyclobutenyl group, a cyclopentenyl group, a cyclohexenyl group, a cyclohexadienyl group or the like. The "bicycloalkyl group" is a group formed by removing one hydrogen from an aliphatic ring having 5 or more carbon atoms of two or more atoms in two rings. Specifically, it is a bicyclo[2.1〇]pentyl group, a bicyclo[2.2.1]heptyl group, a bicyclo[2.2.2]octyl group, and a bicyclo[3.2.1]octyl group. 「 "Aryl" is a monocyclic or polycyclic aromatic carbocyclic group. Containing phenyl, naphthyl, anthracenyl, phenanthryl and the like. Further, it also contains an aryl group which is condensed with other non-aromatic carbocyclic groups. Such as dihydrogenation, nodal, biphenyl, dangerous, tetrahydroindenyl and fluorenyl. Among them, phenyl is preferred. The substituent of the "cycloalkyl group" may be substituted at any position in the ring, such as one or more substituents selected from the group of substituents and the above group of substituents. The substituent group α is composed of: U) halogen; -25- 201032805 (2) pendant oxy group; (3) cyano group; (4) nitro group; (5) imine group which may be substituted by alkyl group or hydroxy group; 6) (i) a hydroxyl group, (ii) an alkyl group, (iii) an alkenyl group, (iv) an alkoxy group, a (v) carboxyl group, which may be substituted by one or more substituents selected from the substituent group 0, respectively. (vi) alkoxycarbonyl, (vii) mercapto, (viii) anthracenyl, (ix) imine, (X) thiol, (xi)alkylthio, (xii)aminecarboxamide, ( Xiii) alkylamine methyl sulfhydryl, (xiv) cycloalkylamine methyl sulfhydryl, (XV) amine thiomethionyl, (xvi) alkylamine methyl sulfhydryl, (xvii) alkylsulfinyl, (xviii) alkane Sulfhydryl, (xix) sulfonyl, (XX) alkylamine sulfonyl, and (xxi) cycloalkylamine sulfonyl, etc.; (7) may be selected from the group consisting of substituent A, alkyl, alkoxy (1) cycloalkyl, (ii) cycloalkenyl, (iii) ring substituted with one or more substituents of an alkyl group, a protected hydroxyalkyl group, a halogenated alkyl group, an alkanesulfonyl group, and an aralkyl sulfonyl group An alkoxy group, (iv) an amine group, and (v) an alkylenedioxy group; and #(8) may be selected from a substituent group /3, an alkyl group, an alkyl halide group, respectively. And (1) phenyl, (ii) naphthyl, (iii) phenoxy, (iv) phenylalkoxy, (v) phenylthio, (vi) phenyl sulfide, substituted with one or more substituents of a pendant oxy group a group, (vii) phenyl azo group, (viii) heterocyclic group, (ix) heterocyclic oxy group, (x) heterocyclic thio group, (Xi) heterocyclic carbonyl group, and (xii) heterocyclic sulfonyl group The group of constituents. The cycloalkyl moiety of "cycloalkylcarbonyl", "cycloalkanolsulfonyl" and "cycloalkoxy" is the same as the above "cycloalkyl". The aryl moiety of "arylsulfonyl" is the same as the above "aryl". -26- 201032805 "Heterocyclyl" is a group derived from a heterocyclic ring having one or more hetero atoms selected from hydrazine, S and N in the ring. For example, a 4 to 8 member ring (preferably a 5 to 7 member ring) or 2 to 3 rings with such ring condensation, and at least one of the rings has 1 to 3 rings, s, and N in the ring. The base derived from the ring of the hetero atom is selected. For example, when a plurality of rings are condensed, they may have a bond in either ring. Specifically, for example, it includes a pyrrolyl group, an imidazolyl group, a pyrazolyl group, a pyridyl group, a pyridazinyl group, a pyrimidinyl group, a pyrazinyl group, a triazolyl group, a tritonyl group, a φ tetrazolyl group, an isoxazolyl group. , carbazolyl, oxadiazolyl, isothiazolyl, thiazolyl, thiadiazolyl, furyl, thienyl, fluorenyl, isodecyl, oxazolyl, indolizinyl, anthraquinone Porphyrin group, isoindolyl group, quinolyl group, isoquinolinyl group, cinnolinyl group, phthalazinyl group, quinalinyl group, naphthyridinyl group, quinoxalinyl group, fluorenyl group, Acridinyl, benzopipetanyl, benzimidazolyl, benzisoxazolyl, benzoxazolyl, benzoxadiazolyl, benzisothiazolyl, benzothiazolyl, benzothiazide Azolyl, benzofuranyl, isobenzofuranyl, fluorenyl benzothiophenyl, benzotriazolyl, imidazolidinyl, triazole pyridyl, imidazothiazolyl, pyridinyl, oxazolinyl, Naphthyridinyl, tetrahydroquinolyl, tetrahydrobenzothiophenyl, miso, AT steep, xanthenyl, phenothiazinyl, phenanthrene Phenoxathiinyl, phenoxazinyl 'dibenzofuranyl, dioxanyl, thiiranyl, oxiranyl, oxathiolanyl, Ϋ́ί azetidinyl, thianyl, 陡 陡 steep, 卩pyrrolidino, imidazolidinyl, imidazolinyl, pyrazolyl, pyrazolinyl, piperidinyl, piperene基-27- 201032805 (piprazinyl), morpholinyl, morpholino, tyrosine thio, N-tyrosylthio, dihydropyridyl, tetrahydrofuranyl, tetrahydropyranyl , tetrahydrothiazolyl, tetrahydroisothiazolyl and the like. Among them, an imidazole group, a benzothiazolyl group, an isothiazolyl group, a benzopiperidyl group, an N-morpholinyl group, a pyridyl group, a quinolyl group, and a pyrimidinyl group are particularly preferable. The substituent of the "heterocyclic group" is exemplified by the same substituent as when the above "cycloalkyl group" is substituted. The heterocyclic group moiety of "heterocyclic oxy group", "heterocyclic thio group", "heterocyclic carbonyl group", and "hetero-cyclosulfonyl group" is the same as the above "heterocyclic group". "Base" includes the following bases. (1) A linear or branched alkylcarbonyl group or an olefinic carbonyl group having 1 to 10 carbon atoms and preferably 1 to 6 carbon atoms and more preferably 1 to 4 carbon atoms. (2) A cycloalkylcarbonyl group having 4 to 9 carbon atoms and preferably 4 to 7 carbon atoms. (3) An aromatic carbonyl group having 7 to 11 carbon atoms. Such as formazan, ethyl, propyl, butyl, isobutyl, pentanyl, trimethylethyl, hexyl, propylene, propynyl, methacryl, croton Crotonoyl, cyclopropylcarbonyl, cyclohexylcarbonyl, cyclooctylcarbonyl, and phenyl(methyl)fluorenyl. The thiol moiety of "oxyl group" is also the same as above. The protecting group of "protectable hydroxyl group" and "protectable hydroxyalkyl group" includes all the hydroxy protecting groups which are usually used. Such as fluorenyl (ethenyl, trichloroethyl, phenyl (methyl) fluorenyl, etc.), alkoxycarbonyl (tertiary butoxycarbonyl, etc.), alkanesulfonyl (methanesulfonyl, etc.), alkoxylated A group (methoxymethyl group, etc.), a trialkyl fluorenyl group (three-28-201032805 grade butylated dimethyl fluorenyl group, etc.). "Halogen" contains fluorine, chlorine, bromine, and iodine. Fluorine and chlorine are preferred. The halogen moiety of "halogenated phenyl" and "halogenated alkyl" is the same as the above "halogen". "Alkyl" is a divalent group connecting 1 to 6 methylene groups. It comprises a divalent group connecting 2 to 6 methylene groups and a divalent group connecting 3 to 6 methylene groups. Such as methylene, ethyl, trimethylene, tetramethylene, pentamethylene, and hexamethylene. Among them, tetramethylene is especially good. The alkylene moiety of the "alkylene dioxyl group" is the same as the above "alkylene group", and is preferably a methylenedioxy group or an ethylenedioxy group. When the compound represented by the formula (I) has an asymmetric carbon atom, it contains a racemate and all stereoisomers (non-image isomers, mirror image isomers, etc.). Further, the compound represented by the formula (I) has one or more double bonds, and when the substituent configuration of the double bond is present in the geometric isomer, all geometric isomers (ie, cis (Z) and trans are included. (E)). φ "Pharmaceutically acceptable salt" may, for example, be a salt of an inorganic acid such as hydrochloric acid, sulfuric acid, nitric acid or phosphoric acid; a salt of an organic acid such as p-toluenesulfonic acid, methanesulfonic acid, oxalic acid or citric acid; ammonium or trimethylammonium; a salt of an organic base such as triethylammonium; an alkali metal salt such as sodium or potassium; and an alkaline earth metal salt such as calcium or magnesium. The "solvate" is a hydrate, an alcoholate or the like of a compound or a salt thereof. For example, 1 hydrate, 2 hydrate, 1 alcoholate, 2 alcoholate, and the like. The prodrug of the compound contained in the pharmaceutical composition of the present invention is included in the range of the compound contained in the pharmaceutical composition of the present invention. -29-201032805 The present invention contains a compound which is a functional derivative of a compound contained in the pharmaceutical composition of the present invention, and is easily converted into a compound contained in the pharmaceutical composition of the invention in a living body. Therefore, the "compound" contained in the pharmaceutical composition of the present invention is a compound specifically expressed by the elements of the pharmaceutical composition of the present invention, or a compound not specifically disclosed, but includes a patient who is administered to an obesity or obesity-related disease. A compound that is converted into a specific compound as described above in a living body. Suitable selection of prodrug derivatives and usual formulation procedures are as described in Design of Prodrugs (ed. H. Bundgaard, Elsevier, 1985), compounds of formula (I) used in the pharmaceutical compositions of the invention, especially The column compound, a pharmaceutically acceptable salt thereof, or a solvate thereof and the like are preferred. *

-30- 201032805

Or Ο

|-Me s /XXr Know. f, UOMe ~ V, 'Oc: cut. ~

Also, the following compounds are more preferred. AOftXCF3 (b)

The weight-inhibiting action of the compound represented by the formula (I) is described in Non-Patent Document 6. Further, Patent Document 5 discloses that the compound represented by the formula (I) exhibits not only an effect of suppressing body weight gain but also an action of suppressing food intake. The compound of the formula (1) used in the above-mentioned pharmaceutical composition of the present invention, which is represented by the formula (1), can be prepared according to the method described in WO01/37826, WO2003/076374, WO2006/001318, and JP-A-2005-255630. . Specifically, for example, the following method can be mentioned.

❹ (where Hal is halogen, other marks are as defined above)

Step A The compound (IV) is reacted with a compound (V) having a substituent R1 corresponding to the target compound in a suitable solvent and in the presence of a base to obtain a compound (II). Solvents such as tetrahydrofuran, dimethylformamide, diethyl ether, dichloromethane, toluene, benzene, xylene, cyclohexane, hexane, chloroform, ethyl acetate, butyl acetate, pentane, heptane, A mixed solvent of dioxane, acetone, acetonitrile, water, and the like. Among them, dioxane and dichloromethane are preferred. As for the base, such as sodium hydroxide, potassium hydroxide, lithium hydroxide and the like. The reaction temperature is about 〇 ° C to 50 ° C and is preferably from about 20 ° C to 30 ° C. The reaction time is from about 5 minutes to 30 hours, and preferably from about 5 to 20 hours. As the compound (IV) and (V), a conventional compound can be used, and a compound synthesized from a conventional compound by a usual method can also be used.

Step B - 32 - 201032805 The compound (II) is reacted with a compound (ΙΠ) having a substituent Z and R2 corresponding to the target compound in a suitable solvent. Solvents such as tetrahydrofuran, dimethylformamide, diethyl ether, dichloromethane, toluene, benzene, xylene, cyclohexane, hexane, chloroform, ethyl acetate, butyl acetate, pentane, heptane, A mixed solvent of dioxane, acetone, acetonitrile, water, and the like. Among them, dimethylformamide, tetrahydrofuran, and ethyl acetate are preferred. If necessary, in 3-di(cycloheximide)methane (also dicyclohexylcarbodiimide), 1-ethyl-3-(3-dimethylamino)carbodiimide (WSCD; water soluble) Equivalent condensing agent and/or acidic additives such as 1-hydroxybenzotriazole, 3,4-dihydro-3-hydroxy-4-sideoxy-1,2,3-benzotrimole The reaction can be carried out in the presence of it. The reaction temperature is about 0 ° C to 50 ° C, and preferably about 20 ° C to 30 ° C. The reaction time is about 5 minutes to 30 hours, and preferably about 5 to 20 hours. φ If necessary, the amine group of the compound may be protected by a conventional method at an appropriate stage of the reaction. As the protecting group, a quinone imine, an alkoxycarbonyl group, an alkoxycarbonyl group, a halogenated alkoxycarbonyl group, an aralkoxycarbonyl group, a trialkylsulfonyl group, an alkanesulfonyl group, a halogenated alkanesulfonyl group, an arylsulfonyl group, an alkylcarbonyl group can be used. , arylcarbonyl and the like. After the protection, the reaction is carried out in each of the above steps, and the treatment is carried out by treatment with an acid or an alkali at an appropriate stage and in a suitable solvent. As the solvent, tetrahydrofuran, dimethylformamide, diethyl ether, dichloromethane, toluene, benzene, xylene, cyclohexane, hexane, chloroform, ethyl acetate, butyl acetate, pentane, heptane can be used. -33- 201032805 Dioxane, acetone, acetonitrile, water, and the like, a base such as hydrazine, pyridine, sodium hydroxide, potassium hydroxide, etc., such as hydrochloric acid, trifluoroacetic acid, hydrogen fluoride, and the like. The pharmaceutical composition of the present invention is useful for preventing or treating diseases such as obesity and obesity-related diseases, and patients suffering from excessive body fat and insufficient exercise to accumulate excess fat in the body. "Obesity" is defined as the state in which too much fat tissue is accumulated. However, there is no correct, simple, and practical method for measuring body fat, and the body mass index (BMI) is used for the height and weight. BMI is defined as the weight (kg) divided by the square of height (meters) (kg/m2). According to the definition of the World Health Organization and the National Institutes of Health in the United States, patients with a BMI of 25 kg/m2 or more were judged to be overweight, and patients above 30 kg/m2 were judged to be obese. However, in the Orientals, when compared with whites, the lower body mass index (BMI) increases the incidence of obesity-related diseases. For example, in Japan, even if the 'φ BMI is about 25 kg/m 2 , there are many patients with diabetes or dyslipidemia such as obesity-related diseases. Therefore, the Japanese Obesity Society defines a BMI of 25 kg/n or more as obesity. Obese patients requiring medical intervention, those with BMI of 30kg/m2 or higher and obesity-related diseases, those with BMI of 30kg/m2 or higher but no obesity-related diseases, or BMI of 25kg/m2 or more and/or visceral fat area (VFA) is 100 cm 2 or more and at least two types of obesity-related diseases occur. Obesity-related diseases such as hypertension, impaired glucose tolerance, diabetes, abnormal fat metabolism, dyslipidemia, hyperuricemia, gout, fatty liver, coronary artery disease, cerebral infarction, etc. The term "obesity" (obesity) in the present specification includes obesity caused by various causes, including genetic or environmental causes. "obesity-related diseases" are diseases caused by obesity, or caused by obesity, or obesity. Obesity-related diseases such as Addephagia, hypertension, impaired glucose tolerance, diabetes, metabolic syndrome, abnormal fat metabolism, arteriosclerosis, hyperuricemia, gout, fatty liver, endometrial cancer, breast cancer, prostate cancer , colorectal cancer, osteoarthritis, low back pain, obstructive sleep-disordered breathing syndrome, coronary artery disease (coronary heart disease), cerebral infarction, menstrual abnormalities, Predwell's syndrome, Fleulich's syndrome, Pickett's syndrome, etc. The pharmaceutical composition of the present invention has a risk of reducing the risk of left ventricular hypertrophy and the secondary result of obesity. Further, the pharmaceutical composition of the present invention is also useful for the treatment of Alzheimer's disease. 0 "Metabolic Syndrome" is defined in the third report (ATP-III) of the "National Cholesterol Education Program Expert Seminar on the Detection, Evaluation and Treatment of High Cholesterol in Adult Blood" (see ESFord et al., JAMA, vol. 287(3), P5 3 6-3 59, January 16, 2002 曰). In short, those with more than three symptoms in abdominal obesity, high blood triglyceride, low HDL cholesterol, high blood pressure, and high fasting blood glucose are defined as metabolic syndrome. "Diabetes" includes insulin-dependent diabetes mellitus (IDDM, type I-35-201032805 diabetes) and non-insulin-dependent diabetes mellitus (NIDDM, both. Type I diabetes is an absolute lack of insulin that regulates glucose utilization. Type 2 diabetes is caused by an inability to respond to insulin, even if the islet burial increases. The second type of diabetes patients are mostly fat medicinal compositions for type 1 diabetes and type 2 saccharide therapy. The pharmaceutical composition of the present invention is also used for gestational sugar or prevention. "Treatment" of obesity and obesity-related diseases, and the weight of obese patients is administered to the medicine of the present invention. When the body weight of the medical group to be administered to the present invention is compared, the patient's body weight may be reduced. The result is that the weight loss can be prevented from being reduced by the previous food therapy and the exercise fruit. The other result of the treatment is φ related disease. The onset and/or severity of treatment. Other shoes that reduce weight or manage weight. Ingestion of whole substances or calories (including reducing the total intake of food or the intake of specific foods such as fats and fats), preventing the decline of the absorption camp, 'the need to reduce the body weight of patients with weight loss or body weight treatment' Incidental sputum I liters lead to changes in metabolic rate and/or can often be limited to a minimum range due to weight loss. Type 2 diabetes), islet is caused by body tissue: secretion is normal or:. The treatment of both sides of the urinary tract of the present invention: the treatment of urinary diseases and/or : for reducing or maintaining sputum. One of the treatments: obesity in front of the body Another treatment of the drug 〖 or drug therapy can reduce obesity ί fruit to be able to maintain [when reducing the patient's food to reduce carbohydrates i, inhibit metabolic rate [management and so on. Anti-metabolism based on 1 ' metabolic rate - 36- 201032805 "Prevention of obesity and obesity-related diseases" means administering the pharmaceutical composition of the present invention to reduce or maintain the body weight of a patient at risk of obesity. One result of this prevention is that the weight of the subject may be reduced when compared to the weight of a patient at risk of obesity before the administration of the pharmaceutical composition of the present invention. Another consequence of this prevention is the ability to prevent a decrease in body weight (i.e., weight management) that is reduced by previous food therapy, exercise, or medication therapy results. Other outcomes of prevention are those with a risk of obesity who can prevent obesity when they are not being treated with obesity. Other outcomes of prevention are those with a risk of obesity who can reduce the onset and/or severity of obesity-related diseases when treated without pre-obesity. The other result of prevention is the ability to prolong the fight against weight gain. The other result of prevention is the ability to prevent further weight gain. Furthermore, the above "treatment" can prevent the onset, progression or severity of obesity-related diseases when starting treatment for obese patients. The pharmaceutical composition of the present invention is a compound having a nutrient absorption and absorption inhibiting effect and a pharmaceutical composition thereof

a pharmaceutical composition obtained by combining a salt of a salt thereof or a solvate thereof, a compound represented by the formula (I), a pharmaceutically acceptable salt thereof or a solvate thereof;

(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or substituted amino group, A substituted or unsubstituted alkoxy group, a substituted or substituted cyclic hydrocarbon group of $-37- 201032805, or a substituted or unsubstituted heterocyclic group). Here, the "combined pharmaceutical composition" includes a form in which each compound is used as a mixture or a form to be administered at the same time. Further, the present invention encompasses a compound having a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof or a solvate thereof, and a compound represented by the formula (I), a pharmaceutically acceptable salt thereof or the like a method for producing the above pharmaceutical composition characterized by mixing;

(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, A substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). In particular, the pharmaceutical composition of the present invention is a compound containing a compound having a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof, or the like, and a compound represented by the formula (I) and a pharmaceutically acceptable compound thereof. a pharmaceutical composition of a compounding agent of a salt or a solvate thereof,

Wherein R1 is alkyl, R2 is hydrogen or alkyl, Z is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or not substituted at -38- 201032805 An amine group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group; and a compound containing a nutrient absorption and absorption inhibiting action thereof a pharmaceutical agent comprising a salt or a solvate thereof, and a pharmaceutical composition comprising a compound represented by the formula (I) and a pharmaceutically acceptable salt thereof or a solvate thereof;

(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, A substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). The pharmaceutical composition of the present invention is not affected by the use of a compound having a nutrient-digesting inhibitor and a pharmaceutically acceptable salt thereof or a solvate thereof, and a compound represented by the formula (I) and a pharmaceutically acceptable salt thereof The amount of the solvate or the like is limited. When the pharmaceutical composition of the present invention is a compounding agent, the compound represented by the formula (I) and a pharmaceutically acceptable salt thereof or a solvate thereof or the like, and a compound having a nutrient absorption and absorption inhibiting action and a pharmaceutically acceptable salt thereof The weight ratio of the solvate or the like thereof is, for example, 100:1 to 1:1 Torr, and preferably 10:1 to 1:10, more preferably 5:1 to 1:5. When the pharmaceutical composition of the present invention is a kit, the formula (I) of the kit represents a compound of -39-201032805 and a pharmaceutically acceptable salt thereof or a solvate thereof, which has a nutrient absorption and absorption inhibitory effect. The weight ratio of the compound and its pharmaceutically acceptable salt or its solvate is, for example, 100:1 to 1:100, and preferably 10:1 to 1:10, more preferably 5:1 to 1:5. . The kit of the pharmaceutical composition of the present invention is as follows, but the present invention is not limited thereto. (a) A kit containing the first oral administration and the second oral administration in the same package: The first oral administration: a compound having a nutrient absorption and absorption inhibiting effect and a pharmaceutically acceptable salt thereof or a mixture of a solvate and a pharmaceutically acceptable carrier and/or excipient, and a second oral administration: a compound represented by the formula (I) and a pharmaceutically acceptable salt thereof or a solvate thereof and the like A pharmaceutically acceptable carrier and/or mixture of excipients. (b) A kit containing a vial for intravenous administration and a vial for intravenous drip in the same package: a compound containing a nutrient absorption and absorption inhibiting compound, a pharmaceutically acceptable salt thereof, or the like, and a pharmaceutically acceptable substance Oral administration of a mixture of a carrier and/or an excipient, and a solvate comprising the compound of the formula (I) and a pharmaceutically acceptable salt thereof or the like, and a pharmaceutically acceptable carrier and/or excipient The mixture was intravenously dripped with a vial. (c) Kits containing the first and second encapsulation chambers in the same package -40-201032805 (infusion package): Package 1: Containing compounds with nutrient absorption and absorption inhibition and their pharmaceutically acceptable salts Or a mixture of a solvate thereof or a pharmaceutically acceptable carrier and/or excipient, a second packaging chamber: a compound comprising the compound represented by the formula (I) and a pharmaceutically acceptable salt thereof or the like A pharmaceutically acceptable carrier and/or mixture of excipients. (d) in the same package: an agent comprising a compound having a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof, or a solvate thereof, and a pharmaceutically acceptable carrier and/or excipient, and A kit for use in conjunction with a method of using a pharmaceutical preparation containing a compound represented by the formula (I) and a pharmaceutically acceptable salt thereof or a solvate thereof. (e) in the same package: a pharmaceutical composition containing a compound of the formula (I), a pharmaceutically acceptable salt thereof, or a solvate thereof, and a pharmaceutically acceptable carrier and/or excipient, and A kit using instructions for the use of a compound having a nutrient absorption and absorption inhibiting action and a pharmaceutically acceptable salt thereof or a solvate thereof. The number of vials and the number of each drug contained in the package of the above kit are indefinite. For example, each vial or each of the medicaments is 1 to 5 pieces. It is preferably 1 to 3 in each vial or each of the medicines. -41 - 201032805 The "agent" in the present specification is a composition containing a compound of an active ingredient. The "oral drug" is an agent that is administered by the oral administration route. When the pharmaceutical composition of the present invention is used in a kit, it is first administered to a medicament containing a compound represented by the formula (I), a pharmaceutically acceptable salt thereof or a solvate thereof, and then administered with a nutrient absorption and absorption inhibition. The acting compound and its pharmaceutically acceptable salt or its solvate may also be used. Further, another form is a drug which is administered to a compound containing a compound having a nutrient absorption and absorption inhibiting action and a pharmaceutically acceptable salt thereof or a solvate thereof, and then administered to a compound containing the formula (I) and A pharmaceutically acceptable salt or a solvate thereof may also be used. Further, another form is a pharmaceutical agent comprising a compound having a nutrient absorption and absorption inhibiting action and a pharmaceutically acceptable salt thereof or a solvate thereof, and a compound represented by the formula (I) and a pharmaceutically acceptable salt thereof Or a solvate agent thereof or the like. The agent for use in the pharmaceutical composition of the present invention can be administered by any method, either by mouth or by Φ. Oral administration can be carried out according to the usual method of preparing tablets, granules, nine doses, liquid preparations, syrups, oral tablets (Backal) agents, or sublingual agents, and the like, and the dosage forms such as muscle administration can be administered by oral administration. Injectables such as intravenous administration, embolization agents, transdermal absorption agents, inhalants, and the like can be suitably administered in any dosage form. The effective amount of the compound (the compound having the nutrient digestion and absorption inhibiting action and the compound represented by the formula (1)) used in the pharmaceutical composition of the present invention may be required to be compatible with an excipient, a binder, a wetting agent, and the like suitable for the dosage form thereof. - 201032805 A pharmaceutical preparation is prepared by mixing various pharmaceutical additives such as a disintegrant, a lubricant, and a diluent. When the injection is prepared, the active ingredient may be sterilized together with an appropriate carrier to prepare a preparation. Excipients such as lactose, white sugar, glucose, starch, calcium carbonate or crystalline cellulose. Binders such as methyl cellulose, carboxymethyl cellulose, hydroxypropyl cellulose, gelatin or polyvinylpyrrolidone. A disintegrating agent such as carboxymethylcellulose, sodium carboxymethylcellulose, starch, sodium sulphate, acacia powder or sodium lauryl sulfate. Lubricants such as talc, magnesium stearate or macrogol. The base of the embolic agent may be cocoa butter, polyethylene glycol or methyl cellulose. When a liquid preparation, an emulsifying (and opaque) or a suspension injection is prepared, a commonly used cosolvent, a suspending agent, an emulsifier, a stabilizer, a preservative, an isotonic agent, or the like can be appropriately added. A flavoring agent, a φ fragrance, or the like may be added during oral administration. The dosage of the pharmaceutical composition used in the pharmaceutical composition of the present invention is preferably set in consideration of the age, weight, type and degree of the disease, the administration route, and the like, and is used as an active ingredient in the present invention when administered orally to an adult. The compound having a nutrient absorption and absorption inhibitory effect of the pharmaceutical composition or the compound represented by the formula (I) is usually from 0.05 to 100 mg/kg/day, and preferably from 0.1 to 50 mg/kg/day. When it is administered orally, it is greatly different depending on the route of administration. The compound which is used as an active ingredient in the pharmaceutical composition of the present invention having the nutrient-43-201032805 digestive absorption-inhibiting effect or the compound represented by the formula (1) is usually 0.005 to 50 mg/ Kg / day, and preferably in the range of H ~ 10mg / kg / day. This can be divided into 1 to several times a day. The kit of the present invention contains nutrient digestion and absorption inhibition When the compound is orlistat, the agent can be administered from about 20 mg to about 1200 mg per day, and from about 60 mg to about 600 mg, preferably from about 20 mg to about 4, in one or three or one continuous release forms per day. More preferably, it is more preferably 00 mg. It is more preferred to administer 120 mg of the agent to the drug once a day or in a continuous release form. The kit of the present invention contains the agent of orlistat, as described in U.S. Patent No. 6,004,996. The method of using the pharmaceutical composition of the present invention is, for example, the following, but the present invention is not limited thereto. (1) A compound having a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof, or the like , and the combination of formula (I) And a pharmaceutically acceptable salt thereof or a solvate thereof, etc., as a part of the same medicament, a method for the prophylaxis or treatment of obesity or obesity-related diseases (administered by the above-mentioned compounding agent) (2) An agent containing a compound having a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof, or a solvate thereof, and a compound containing the compound represented by the formula (1) and a pharmaceutical thereof, which are part of an appropriate administration plan for the purpose of obtaining a combination therapeutic benefit A method for the prevention or treatment of obesity or obesity-related diseases to which the above-mentioned salt or its solvate is administered separately (using the prevention or treatment method of the above kit). -44- 201032805 Appropriate administration plan, each administration The dosage of the drug and the specific administration interval of each agent are determined according to the specific combination of the agent to be used, the severity of the patient's condition and the severity of the disease, etc. The administration plan may be, for example, the following, but the invention is not limited thereto. Drug administration plan for pharmaceutical composition. (1) Compounds with nutrient digestion and absorption inhibition and their pharmaceutically acceptable A compound of a salt or a solvate thereof and a compound represented by the formula (I), and a pharmaceutically acceptable salt thereof or a solvate thereof, are administered once or three times a day. (2) Formula ( I) a compound represented by the compound and a pharmaceutically acceptable salt thereof or a solvate thereof, and a pharmaceutical agent comprising a compound having a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof, or a solvate thereof, etc. (1) A pharmaceutical agent containing a compound represented by the formula (I) and a pharmaceutically acceptable salt thereof or a solvate thereof, is administered once a day, and contains nutrients. The drug for the absorption inhibiting compound and the pharmaceutically acceptable salt thereof or the solvate thereof is administered once to three times a day. (4) A pharmaceutical composition containing a compound represented by the formula (I), a pharmaceutically acceptable salt thereof or a solvate thereof, and a pharmaceutical composition containing the compound of the formula (I) and a pharmaceutical thereof after several days to several weeks An agent for a salt or a solvate thereof, and a drug comprising a compound having a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof, or a solvate thereof. (5) First, a drug containing a compound having a nutrient absorption and absorption inhibiting action -45 - 201032805 and a pharmaceutically acceptable salt thereof or a solvate thereof, and containing the formula (I) after several days to several weeks An agent for a compound and a pharmaceutically acceptable salt thereof or a solvate thereof, and a drug comprising a compound having a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof, or a solvate thereof. The pharmaceutical composition of the present invention can be used in combination with other anti-obesity agents. Further, the drug therapy according to the pharmaceutical composition of the present invention can also be combined with food therapy, exercise therapy and other drug therapy. "Picking therapy" such as diet therapy, low-calorie diet (LCD) therapy, very low calorie diet (VLCD) therapy, and calorie-reducing diet (RCD) therapy. "Diet Diet Therapy" is a mild diet that inhibits daily calorie intake at a level of 1200 kcal. "Low-calorie diet therapy" is a foraging therapy that limits calorie intake to about 600 to 1200 kcal per day. For example, the low-calorie is taken in a well-balanced foraging diet, or the low-calorie is ingested by a diet rich in special nutrients such as high-fat, low-calorie foraging, high-protein low-calorie diet, and the like. "Very Low Calorie Foraging Therapy" is a foraging therapy that limits calorie intake to about 2 to 600 calories per day. A half-stardication therapy for severely obese patients. "Reducing calorie diet therapy" is a dieting therapy that takes about 800 calories per day from the basic metabolism. When the pharmaceutical composition of the present invention is used in combination with an anti-obesity therapy, various administration plans can be used, and the following are exemplified below. -46 - 201032805 (1) At the same time, diet therapy and/or exercise therapy and drug therapy using the pharmaceutical composition of the present invention are started. (2) The foraging therapy and/or exercise therapy is carried out for several days to several weeks, and after a certain degree of weight reduction, the drug therapy using the pharmaceutical composition of the present invention is started. Further, the present invention also encompasses the following forms. a step of administering a compound having a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof, or a solvate thereof, in combination with a compound represented by the formula (I), a pharmaceutically acceptable salt thereof, or a solvate thereof a method of inducing or promoting weight loss, or maintaining or managing body weight;

(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted aryl group, A substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). The pharmaceutical composition of the present invention contains a compound having a nutrient absorption and absorption inhibiting action and a compound represented by the formula (I), which respectively exhibit a function of inhibiting body weight, promoting the effect of inhibiting body weight, and/or maintaining or managing body weight by different action mechanisms. The role. Furthermore, the present invention also encompasses the following forms. An agent comprising a compound having a nutrient absorption and absorption inhibiting action and a pharmaceutically acceptable salt thereof or a solvate thereof, wherein the compound of the formula (I) is represented by the compound -47-201032805 and a pharmaceutically acceptable salt thereof or An enhancer for the prophylactic or therapeutic effect of obesity or sulphate-related diseases;

(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, A substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). An agent comprising a compound represented by the formula (I), a pharmaceutically acceptable salt thereof, or a solvate thereof, etc., which comprises a compound having a nutrient absorption and absorption inhibiting action and a pharmaceutically acceptable salt thereof or a solvate thereof, etc. An enhancer for the prevention or treatment of obesity or obesity-related diseases;

(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, A substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). A compound having a nutrient absorption and absorption inhibiting action and a pharmaceutically acceptable salt thereof or a solvate thereof, which can enhance the obesity or obesity of the compound represented by the formula (I) and a pharmaceutically acceptable salt thereof or a solvate thereof or the like The prevention or treatment effect of related diseases. A compound represented by the formula (I) and a pharmaceutically acceptable salt thereof, which is a pharmaceutically acceptable salt of -48-201032805, or a solvate thereof, which is capable of enhancing a compound having a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof, or the like The preventive or therapeutic effect of obesity or obesity-related diseases. Therefore, the pharmaceutical composition of the present invention can prevent or treat obesity or obesity-related diseases with great efficiency as compared with when each compound is used alone. Hereinafter, the present invention will be described in detail using an example in which orlistat is a compound having a nutrient absorption and absorption inhibiting effect and a compound (a) is a compound represented by the formula (I), but the present invention is not limited thereto. . 0 Example 1 7-week-old male C57BL/6J mice (body weight: 20.4 to 24.2 kg; purchased from CLEA, Japan) were fed with a high-fat diet (manufactured by Test Diet Co., Ltd.) for 5 weeks to induce obesity. Next, a 0.5% aqueous solution of hydroxypropylmethylcellulose (manufactured by Shin-Etsu Chemical Co., Ltd.) was orally administered twice a day (8:30 - 11:00 am, 14:30 - 17:00 pm). 4 weeks, by domestication to adapt to this operation. The following six groups were classified according to the body weight of the mice and the average body weight change during the 4-week acclimation period. That is: (1) control group (0.5% hydroxypropyl methylcellulose l〇ml/kg); (2) Compound® (a) 50 mg/kg group; (3) Orlistat 12.5 mg/kg group (4) Orlistat 25 mg/kg Group: (5) Compound (a) 50 mg/kg + Orlistat 12.5 mg/kg group; (6) Compound (a) 50 mg/kg + Orlistat 25 mg/ Kg group. Each group was administered for 4 weeks on a one-time basis (8:30 to 11:00 am, 15:00 to 18:00 pm). The body weight of the mice at the start of administration was 30.1 to 34.9 g. The results of 4 weeks of continuous administration were compared with the control group. (2) Compound (a) 50 mg/kg group inhibited 〇.9 g; (3) Orlistat 12.5 mg/kg group inhibited 0.6 g; (4) The lesitastat 25 mg/kg group inhibited 2.1 g. For each group administered together, Bay [J (5) -49- 201032805 Compound (a) 50 mg / kg + orlistat 12.5 mg / kg group inhibited 2.5 g; (6) Compound (a) 50 mg / kg + Orly The statin 25 mg/kg group inhibited 4.2 g. From the results, it was found that the compound (a) had a weight-inhibiting effect when it was co-administered with orlistat. That is, the effect of the addition is obtained when compared with the sum of the individual effects of the respective drugs (refer to Fig. 1 and Fig. 2. The compound (a) in the second figure + orlistat means the compound (a) 5 0 mg / kg + orlistat 2 5 mg / kg). On the other hand, when compared with the control group for 4 weeks of food intake (2) Compound (a) 50 mg/kg group inhibited 2.5 g; (3) Orlistat 12.5 mg/kg group increased by 7.6 g; (4) The amount of the booster 25mg/kg group was 14.5g. For each group administered together, (5) compound (a) 50 mg / kg + orlistat 1 2 · 5 mg / kg group increased by 7.4 g; (6) compound (a) 50 mg / kg + Ollie The statin 25mg/kg group increased by 8.4g. These results indicate that the food intake caused by orlistat is inhibited by co-administration of compound U). [Possibility of Industrial Applicability] The pharmaceutical composition of the present invention is very useful as a therapeutic or prophylactic agent for obesity or obesity-related diseases. Moreover, the pharmaceutical composition is very useful in the management of body weight of obesity. [Simplified illustration] Fig. 1: Changes in cumulative body weight at 4 weeks of administration in obese model mice. Figure 2: Difference in body weight between control group and treatment group at the end of the test [Explanation of main component symbols] None. -50-

Claims (1)

201032805 * VII. Patent application scope: 1. A pharmaceutical composition which is a compound having a nutrient absorption and absorption inhibiting effect, a pharmaceutically acceptable salt thereof or a solvate thereof, and a compound represented by the formula (1) a pharmaceutical composition comprising a pharmaceutically acceptable salt or a solvate thereof; 10 (wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, A substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). 2. A pharmaceutical composition as claimed in claim 1 which is a compounding agent. 3. The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition comprises a pharmaceutical composition comprising a compound having a nutrient absorption and absorption inhibiting action and a pharmaceutically acceptable salt thereof or a solvate thereof; I) a kit of the indicated compound and its pharmaceutically acceptable salt or a solvate thereof; (wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, wherein Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, A substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group of -51 - 201032805, or a substituted or unsubstituted heterocyclic group). 4. The pharmaceutical composition according to any one of claims 3 to 3, wherein the compound having a nutrient absorption and absorption inhibiting action is a compound having a fat absorption inhibiting action. 5. The pharmaceutical composition according to claim 4, wherein the compound having a fat absorption inhibiting action is a compound having a pancreatic lipase inhibiting action. 6. The pharmaceutical composition according to claim 5, wherein the compound having pancreatic lipase inhibitory action is Orlistat. 7. The pharmaceutical composition according to any one of claims 1 to 6, wherein the compound represented by the formula (I) is a compound represented by the following formula (a) (a) The pharmaceutical composition according to any one of claims 1 to 7, which is for the purpose of preventing or treating weight management for obesity or obesity-related diseases or obesity. 9 · The pharmaceutical composition of claim 8 of the patent scope, wherein obesity-related diseases are Addephagia, hypertension, impaired glucose tolerance, diabetes, metabolic syndrome, abnormal fat metabolism, arteriosclerosis, hyperuricemia, gout , fatty liver, endometrial cancer, breast cancer, prostate cancer, colorectal cancer, osteoarthritis, low back pain, obstructive sleep apnea syndrome, coronary artery disease, cerebral infarction, menstrual abnormalities, Predwell's syndrome (Prader-Willi Syndrome), Fleulich syndrome - 52- 201032805 Group (Froehlich Syndrome), or Pickwickian Syndrome 〇 10. - The preventive or therapeutic effect of obesity or obesity-related diseases The enhancer' contains the compound represented by the formula (I) and a pharmaceutically acceptable salt thereof or a solvate thereof; Ζ is substituted or $ (wherein R1 is a hospital group, R2 is a hydrogen atom or a deutero group, a substituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amine group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group, and a compound having a nutrient absorption and absorption inhibiting effect and a pharmaceutically acceptable amount thereof An agent for a salt or a solvate thereof. 1 1 · An agent for the prevention or treatment of obesity or obesity-related diseases of a medicament, which comprises a compound represented by the formula (1) and a pharmaceutical agent thereof, or a solvate thereof, which is pharmaceutically acceptable, (wherein R 1 is an alkyl group, R 2 is a hydrogen atom or an alkyl group, and Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, a substituted or unsubstituted alkoxy group, a substituted or substituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group; &1 having a nutrient digestion and absorption inhibiting compound and a pharmaceutical thereof -53- 201032805 The permissible salt or its solvate. 12. An agent comprising a compound having a nutrient absorption and absorption inhibiting action and a pharmaceutically acceptable salt thereof or a solvate thereof, which is used for the compound containing the compound represented by the formula (I) and a pharmaceutically acceptable salt thereof Or a solvate for its use; (wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, A substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). 13. A pharmaceutical agent comprising a compound represented by the formula (I), a pharmaceutically acceptable salt thereof, or a solvate thereof, which is used in combination with a compound having a nutrient absorption and absorption inhibiting action and a pharmaceutically acceptable salt thereof Or a solvate for its use; (wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, A substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). 14. The medicament according to claim 12 or 13 for use in the prevention or treatment of obesity or obesity-related diseases or the weight management of obesity is -54-201032805. A method for producing a pharmaceutical composition according to claim 1, which is characterized in that a compound having a nutrient absorption and absorption inhibiting action and a pharmaceutically acceptable salt thereof or a solvate thereof, and the formula (I) a compound represented by the compound and a pharmaceutically acceptable salt thereof or a solvate thereof, etc., (wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, A substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group).